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Cysts originating from cervical lymphatic ducts are very seldom affections. However, they play an important role in the differential diagnosis of supraclavicular masses. The etiology remains unclear. Practically all cases arise from the thoracic duct, those affecting the right lymphatic duct are encountered exceptionally rarely. The cysts manifest themselves clinically as an otherwise asymptomatic swelling in the supraclavicular area. The diagnostics is based on imaging methods. However, both the CT and MRI scans lack any specific feature. In some cases, a direct communication between the cyst and relevant duct can be demonstrated using a lymphangiography. In a lab analysis, high content of T lymphocytes and triglyceride level is pathognomonic. In the differential diagnosis of these cyst the main problem is posed by so called unilocular lymphatic cysts, which share practically identical histomorphology, but they lack communication with a lymphatic duct. There is not a uniform opinion on the therapy. Because of absolute benign nature and possibility of spontaneous regression of these cysts, wait and see strategy is an option. A successful sclerotization was reported. The majority of authors prefer surgical exstirpation. At the operation, lymphatic vessels entering the cyst must be ligated to prevent the chyle leakage. In the presented overview, etiological, pathomorphological and clinical aspects of the cervical lymphatic duct cysts are described in detail. [ABSTRACT FROM AUTHOR]

TGFβ has roles in inflammation, wound healing, epithelial to mesenchymal transition (EMT), and cancer stem cell states, and acts as a tumor suppressor gene for squamous cell carcinoma (SCC). SCCs are also characterized by high levels of ΔNp63, which induces epithelial cell phenotypes and maintains squamous stem cells. Previous studies indicate a complex interplay between ΔNp63 and TGFβ signaling, with contradictory effects reported. We investigated the effects of TGFβ on p63 isoform proteins and mRNAs in non-malignant squamous and SCC cells, and the role of either canonical or non-canonical TGFβ signaling pathways. TGFβ selectively increased ΔNp63 protein levels in non-malignant keratinocytes in association with SMAD3 activation and was prevented by TGFβ receptor inhibition, indicating activation of canonical TGFβ pathway signaling. TP63 isoform mRNAs showed discordance from protein levels, with an initial increase in both TAP63 and ΔNP63 mRNAs followed by a decrease at later times. These data demonstrate complex and heterogeneous effects of TGFβ in squamous cells that depend on the extent of canonical TGFβ pathway aberrations. The interplay between TGFβ and p63 is likely to influence the magnitude of EMT states in SCC, with clinical implications for tumor progression and response to therapy., (© 2024. The Author(s).)

Efficient separation and sensitive identification of pathogenic bacterial strains is essential for a prosperous modern society, with direct applications in medical diagnostics, drug discovery, biodefense, and food safety. We developed a fast and reliable method for antibody-based selective immobilization of bacteria from suspension onto a gold-plated glass surface, followed by detection using strain-specific antibodies linked to gold nanoparticles decorated with a reporter molecule. The reporter molecules are subsequently detected by surface-enhanced Raman spectroscopy (SERS). Such a multi-functionalized nanoparticle is called a SERS-tag. The presented procedure uses widely accessible and cheap materials for manufacturing and functionalization of the nanoparticles and the immobilization surfaces. Here, we exemplify the use of the produced SERS-tags for sensitive single-cell detection of opportunistic pathogen Escherichia coli, and we demonstrate the selectivity of our method using two other bacterial strains, Staphylococcus aureus and Serratia marcescens , as negative controls. We believe that the described approach has a potential to inspire the development of novel medical diagnostic tools for rapid identification of bacterial pathogens.

Angiotensin-converting enzyme inhibitors (ACEis) have been used to treat anthracycline (ANT)-induced cardiac dysfunction, and they appear beneficial for secondary prevention in high-risk patients. However, it remains unclear whether they truly prevent ANT-induced cardiac damage and provide long-lasting cardioprotection. The present study aimed to examine the cardioprotective effects of perindopril on chronic ANT cardiotoxicity in a rabbit model previously validated with the cardioprotective agent dexrazoxane (DEX) with focus on post-treatment follow-up (FU). Chronic cardiotoxicity was induced by daunorubicin (DAU; 3 mg/kg/week for 10 weeks). Perindopril (0.05 mg/kg/day) was administered before and throughout chronic DAU treatment. After the completion of treatment, significant benefits were observed in perindopril co-treated animals, particularly full prevention of DAU-induced mortality and prevention or significant reductions in cardiac dysfunction, plasma cardiac troponin T (cTnT) levels, morphological damage, and most of the myocardial molecular alterations. However, these benefits significantly waned during 3 weeks of drug-free FU, which was not salvageable by administering a higher perindopril dose. In the longer (10-week) FU period, further worsening of left ventricular function and morphological damage occurred together with heart failure (HF)-related mortality. Continued perindopril treatment in the FU period did not reverse this trend but prevented HF-related mortality and reduced the severity of the progression of cardiac damage. These findings contrasted with the robust long-lasting protection observed previously for DEX in the same model. Hence, in the present study, perindopril provided only temporary control of ANT cardiotoxicity development, which may be associated with the lack of effects on ANT-induced and topoisomerase II β (TOP2B)-dependent DNA damage responses in the heart., (© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Background: Anthracycline-induced heart failure has been traditionally attributed to direct iron-catalyzed oxidative damage. Dexrazoxane (DEX)-the only drug approved for its prevention-has been believed to protect the heart via its iron-chelating metabolite ADR-925. However, direct evidence is lacking, and recently proposed TOP2B (topoisomerase II beta) hypothesis challenged the original concept., Methods: Pharmacokinetically guided study of the cardioprotective effects of clinically used DEX and its chelating metabolite ADR-925 (administered exogenously) was performed together with mechanistic experiments. The cardiotoxicity was induced by daunorubicin in neonatal ventricular cardiomyocytes in vitro and in a chronic rabbit model in vivo (n=50)., Results: Intracellular concentrations of ADR-925 in neonatal ventricular cardiomyocytes and rabbit hearts after treatment with exogenous ADR-925 were similar or exceeded those observed after treatment with the parent DEX. However, ADR-925 did not protect neonatal ventricular cardiomyocytes against anthracycline toxicity, whereas DEX exhibited significant protective effects (10-100 µmol/L; P <0.001). Unlike DEX, ADR-925 also had no significant impact on daunorubicin-induced mortality, blood congestion, and biochemical and functional markers of cardiac dysfunction in vivo (eg, end point left ventricular fractional shortening was 32.3±14.7%, 33.5±4.8%, 42.7±1.0%, and 41.5±1.1% for the daunorubicin, ADR-925 [120 mg/kg]+daunorubicin, DEX [60 mg/kg]+daunorubicin, and control groups, respectively; P <0.05). DEX, but not ADR-925, inhibited and depleted TOP2B and prevented daunorubicin-induced genotoxic damage. TOP2B dependency of the cardioprotective effects was probed and supported by experiments with diastereomers of a new DEX derivative., Conclusions: This study strongly supports a new mechanistic paradigm that attributes clinically effective cardioprotection against anthracycline cardiotoxicity to interactions with TOP2B but not metal chelation and protection against direct oxidative damage.

This paper focuses on the research and development of a suitable method for creating a selective emitter for the visible and near-infrared region to be able to work optimally together with silicon photovoltaic cells in a thermophotovoltaic system. The aim was to develop a new method to create very fine structures beyond the conventional standard (nanostructures), which will increase the emissivity of the base material for it to match the needs of a selective emitter for the VIS and NIR region. Available methods were used to create the nanostructures, from which we eliminated all unsuitable methods; for the selected method, we established the optimal procedure and parameters for their creation. The development of the emitter nanostructures included the necessary substrate pretreatments, where great emphasis was placed on material purity and surface roughness. Tungsten was purposely chosen as the main material for the formation of the nanostructures; we verified the effect of the formed structure on the resulting emissivity. This work presents a new method for the formation of nanostructures, which are not commonly formed in such fineness; by this, it opens the way to new possibilities for achieving the desired selectivity of the thermophotovoltaic emitter.

The p53 family member p63 exists as two major protein variants (TAp63 and ΔNp63) with distinct expression patterns and functional properties. Whilst downstream target genes of p63 have been studied intensively, how p63 variants are themselves controlled has been relatively neglected. Here, we review advances in understanding ΔNp63 and TAp63 regulation, highlighting their distinct pathways. TAp63 has roles in senescence and metabolism, and in germ cell genome maintenance, where it is activated post-transcriptionally by phosphorylation cascades after DNA damage. The function and regulation of TAp63 in mesenchymal and haematopoietic cells is less clear but may involve epigenetic control through DNA methylation. ΔNp63 functions to maintain stem/progenitor cells in various epithelia and is overexpressed in squamous and certain other cancers. ΔNp63 is transcriptionally regulated through multiple enhancers in concert with chromatin modifying proteins. Many signalling pathways including growth factors, morphogens, inflammation, and the extracellular matrix influence ΔNp63 levels, with inconsistent results reported. There is also evidence for reciprocal regulation, including ΔNp63 activating its own transcription. ΔNp63 is downregulated during cell differentiation through transcriptional regulation, while post-transcriptional events cause proteasomal degradation. Throughout the review, we identify knowledge gaps and highlight discordances, providing potential explanations including cell-context and cell-matrix interactions. Identifying individual p63 variants has roles in differential diagnosis and prognosis, and understanding their regulation suggests clinically approved agents for targeting p63 that may be useful combination therapies for selected cancer patients. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (© 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Bisdioxopiperazine agent dexrazoxane (ICRF-187) has been the only effective and approved drug for prevention of chronic anthracycline cardiotoxicity. However, the structure-activity relationships (SARs) of its cardioprotective effects remain obscure owing to limited investigation of its derivatives/analogs and uncertainties about its mechanism of action. To fill these knowledge gaps, we tested the hypothesis that dexrazoxane derivatives exert cardioprotection via metal chelation and/or modulation of topoisomerase II β (Top2B) activity in chronic anthracycline cardiotoxicity. Dexrazoxane was alkylated in positions that should not interfere with the metal-chelating mechanism of cardioprotective action; that is, on dioxopiperazine imides or directly on the dioxopiperazine ring. The protective effects of these agents were assessed in vitro in neonatal cardiomyocytes. All studied modifications of dexrazoxane molecule, including simple methylation, were found to abolish the cardioprotective effects. Because this challenged the prevailing mechanistic concept and previously reported data, the two closest derivatives [(±)-4,4'-(propane-1,2-diyl)bis(1-methylpiperazine-2,6-dione) and 4-(2-(3,5-dioxopiperazin-1-yl)ethyl)-3-methylpiperazine-2,6-dione] were thoroughly scrutinized in vivo using a rabbit model of chronic anthracycline cardiotoxicity. In contrast to dexrazoxane, both compounds failed to protect the heart, as demonstrated by mortality, cardiac dysfunction, and myocardial damage parameters, although the pharmacokinetics and metal-chelating properties of their metabolites were comparable to those of dexrazoxane. The loss of cardiac protection was shown to correlate with their abated potential to inhibit and deplete Top2B both in vitro and in vivo. These findings suggest a very tight SAR between bisdioxopiperazine derivatives and their cardioprotective effects and support Top2B as a pivotal upstream druggable target for effective cardioprotection against anthracycline cardiotoxicity. SIGNIFICANCE STATEMENT: This study has revealed the previously unexpected tight structure-activity relationships of cardioprotective effects in derivatives of dexrazoxane, which is the only drug approved for the prevention of cardiomyopathy and heart failure induced by anthracycline anticancer drugs. The data presented in this study also strongly argue against the importance of metal-chelating mechanisms for the induction of this effect and support the viability of topoisomerase II β as an upstream druggable target for effective and clinically translatable cardioprotection., Competing Interests: Conflict of interest: None declared., (Copyright © 2020 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: An emerging body of research has begun to elucidate disturbances to social cognition in specific personality disorders (PDs). No research has been conducted on patients with Mixed Personality Disorder (MPD), however, who meet multiple diagnostic criteria. Further, very few studies have compared social cognition between patients with PD and those presenting with symptomatic diagnoses that co-occur with personality pathologies, such as anxiety disorder (AD). The aim of this study was to provide a detailed characterization of deficits to various aspects of social cognition in MPD and dissociate impairments specific to MPD from those exhibited by patients with AD who differ in the severity of personality pathology., Method: Building on our previous research, we administered a large battery of self-report and performance-based measures of social cognition to age-, sex- and education-matched groups of patients with MPD or AD, and healthy control participants (HCs; n = 29, 23, and 54, respectively). This permitted a detailed profiling of these clinical groups according to impairments in emotion recognition and regulation, imitative control, low-level visual perspective taking, and empathic awareness and expression., Results: The MPD group demonstrated poorer emotion recognition for negative facial expressions relative to both HCs and AD. Compared with HCs, both clinical groups also performed significantly worse in visual perspective taking and interference resolution, and reported higher personal distress when empathizing and more state-oriented emotion regulation., Conclusion: We interpret our results to reflect dysfunctional cognitive control that is common to patients with both MPD and AD. Given the patterns of affective dispositions that characterize these two diagnostic groups, we suggest that prolonged negative affectivity is associated with inflexible styles of emotion regulation and attribution. This might potentiate the interpersonal dysfunction exhibited in MPD, particularly in negatively valenced and challenging social situations., (Copyright © 2020 Czekóová, Shaw, Pokorná and Brázdil.)

Dexrazoxane (DEX), the only cardioprotectant approved against anthracycline cardiotoxicity, has been traditionally deemed to be a prodrug of the iron-chelating metabolite ADR-925. However, pharmacokinetic profile of both agents, particularly with respect to the cells and tissues essential for its action (cardiomyocytes/myocardium), remains poorly understood. The aim of this study is to characterize the conversion and disposition of DEX to ADR-925 in vitro (primary cardiomyocytes) and in vivo (rabbits) under conditions where DEX is clearly cardioprotective against anthracycline cardiotoxicity. Our results show that DEX is hydrolyzed to ADR-925 in cell media independently of the presence of cardiomyocytes or their lysate. Furthermore, ADR-925 directly penetrates into the cells with contribution of active transport, and detectable concentrations occur earlier than after DEX incubation. In rabbits, ADR-925 was detected rapidly in plasma after DEX administration to form sustained concentrations thereafter. ADR-925 was not markedly retained in the myocardium, and its relative exposure was 5.7-fold lower than for DEX. Unlike liver tissue, myocardium homogenates did not accelerate the conversion of DEX to ADR-925 in vitro, suggesting that myocardial concentrations in vivo may originate from its distribution from the central compartment. The pharmacokinetic parameters for both DEX and ADR-925 were determined by both noncompartmental analyses and population pharmacokinetics (including joint parent-metabolite model). Importantly, all determined parameters were closer to human than to rodent data. The present results open venues for the direct assessment of the cardioprotective effects of ADR-925 in vitro and in vivo to establish whether DEX is a drug or prodrug., (Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.)

Chronic anthracycline (ANT) cardiotoxicity is a serious complication of cancer chemotherapy. Molsidomine, a NO-releasing drug, has been found cardioprotective in different models of I/R injury and recently in acute high-dose ANT cardiotoxicity. Hence, we examined whether its cardioprotective effects are translatable to chronic ANT cardiotoxicity settings without induction of nitrosative stress and interference with antiproliferative action of ANTs. The effects of molsidomine (0.025 and 0.5mg/kg, i.v.) were studied on the well-established model of chronic ANT cardiotoxicity in rabbits (daunorubicin/DAU/3mg/kg/week for 10 weeks). Molsidomine was unable to significantly attenuate mortality, development of heart failure and morphological damage induced by DAU. Molsidomine did not alter DAU-induced myocardial lipoperoxidation, MnSOD down-regulation, up-regulation of HO-1, IL-6, and molecular markers of cardiac remodeling. Although molsidomine increased 3-nitrotyrosine in the myocardium, this event had no impact on cardiotoxicity development. Using H9c2 myoblasts and isolated cardiomyocytes, it was found that SIN-1 (an active metabolite of molsidomine) induces significant protection against ANT toxicity, but only at high concentrations. In leukemic HL-60 cells, SIN-1 initially augmented ANT cytotoxicity (in low and clinically achievable concentrations), but it protected these cells against ANT in the high concentrations. UHPLC-MS/MS investigation demonstrated that the loss of ANT cytotoxicity after co-incubation of the cells in vitro with high concentrations of SIN-1 is caused by unexpected chemical depletion of DAU molecule. The present study demonstrates that cardioprotective effects of molsidomine are not translatable to clinically relevant chronic form of ANT cardiotoxicity. The augmentation of antineoplastic effects of ANT in low (nM) concentrations may deserve further study., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Dexrazoxane (DEX) is a clinically available cardioprotectant that reduces the toxicity induced by anthracycline (ANT) anticancer drugs; however, DEX is seldom used and its action is poorly understood. Inorganic nitrate/nitrite has shown promising results in myocardial ischemia-reperfusion injury and recently in acute high-dose ANT cardiotoxicity. However, the utility of this approach for overcoming clinically more relevant chronic forms of cardiotoxicity remains elusive. Hence, in this study, the protective potential of inorganic nitrate and nitrite against chronic ANT cardiotoxicity was investigated, and the results were compared to those using DEX. Chronic cardiotoxicity was induced in rabbits with daunorubicin (DAU). Sodium nitrate (1g/L) was administered daily in drinking water, while sodium nitrite (0.15 or 5mg/kg) or DEX (60mg/kg) was administered parenterally before each DAU dose. Although oral nitrate induced a marked increase in plasma NOx, it showed no improvement in DAU-induced mortality, myocardial damage or heart failure. Instead, the higher nitrite dose reduced the incidence of end-stage cardiotoxicity, prevented related premature deaths and significantly ameliorated several molecular and cellular perturbations induced by DAU, particularly those concerning mitochondria. The latter result was also confirmed in vitro. Nevertheless, inorganic nitrite failed to prevent DAU-induced cardiac dysfunction and molecular remodeling in vivo and failed to overcome the cytotoxicity of DAU to cardiomyocytes in vitro. In contrast, DEX completely prevented all of the investigated molecular, cellular and functional perturbations that were induced by DAU. Our data suggest that the difference in cardioprotective efficacy between DEX and inorganic nitrite may be related to their different abilities to address a recently proposed upstream target for ANT in the heart - topoisomerase IIβ., (Copyright © 2015. Published by Elsevier Ltd.)

It was previously believed that larger metal nanoparticles behave as tiny mirrors that are pushed by the light beam radiative force along the direction of beam propagation, without a chance to be confined. However, several groups have recently reported successful optical trapping of gold and silver particles as large as 250 nm. We offer a possible explanation based on the fact that metal nanoparticles naturally occur in various non-spherical shapes and their optical properties differ significantly due to changes in localized plasmon excitation. We demonstrate experimentally and support theoretically three-dimensional confinement of large gold nanoparticles in an optical trap based on very low numerical aperture optics. We showed theoretically that the unique properties of gold nanoprisms allow an increase of trapping force by an order of magnitude at certain aspect ratios. These results pave the way to spatial manipulation of plasmonic nanoparticles using an optical fibre, with interesting applications in biology and medicine.

Scanning Low Energy Electron Microscopy (SLEEM) is an imaging technique which uses low energy electrons while providing a very good image resolution. Reflectivity of very slow electrons in the range 0-30 eV can be correlated with the electronic structure of the material, aiming at the determination of the local crystallographic orientation. Since SLEEM is a 2D imaging method, a suitable algorithm is needed to pre-process the image data depending on the beam energy as the third dimension. The crucial task is to detect grain boundaries in polycrystals and evaluate the image signal in connection to the energy of electron impact. Recent algorithms performing the task for the traditional EBSD method are not suitable as they do not address the side-effects of the SLEEM technique. We propose a method that detects the grain boundaries while correcting for image distortion caused by the variation of cathode lens strength, and for several other issues., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Study Aim: To determine antibiotic resistance and incidence of multidrug resistance among Nontyphoidal salmonellae serovars isolated from humans., Material and Methods: Consecutive Salmonella isolates from patients, recovered in 48 microbiology laboratories in May 2012, were analyzed in the respective reference laboratories at the National Institute of Public Health. Strains were re-identified and differentiated into serovars. Their minimum inhibitory concentrations (MICs) to 11 antibiotics were determined by the microdilution method., Results: Of 25 serovars identified among 637 strains of Salmonella enterica, the most frequent were Enteritidis (87.0 %), Typhimurium (4.9 %), and monophasic Typhimurium 4,[5],12:i:- (2.0 %) and Mbandaka (0.6 %); other serovars were rare. Altogether 558 strains (87.6 %) were susceptible to all antibiotics tested and the remaining 79 strains were resistant to one or more antibiotics. The prevalence rates of resistance to individual antibiotics among 637 study strains were as follows: ampicillin 8.5%, tetracycline 5.7%, sulfamethoxazole 5.2%, cipro-floxacin 3.8%, and chloramphenicol 2.5%. Resistance to gentamicin, trimethoprim, and third and fourth generation cephalosporins was rare ( 0.5%) and none of the study strains showed resistance to meropenem. Three producers of extended spectrum beta-lactamase were multidrug resistant and two of them recovered from twins exhibited a different pattern of resistance. Resistant strains were most often assigned to the following serovars: Enteritidis (49.4%), Typhimurium (26.6%), and monophasic Typhimurium (15.2%). While only 7% (39 of 554 strains) of Enteritidis strains were resistant, the serovars Typhimurium and its monophasic variant 4,[5],12:i:- showed high rates of resistance, i.e. 66.7 and 92.3%, respectively. Furthermore, resistance was revealed in all strains of the serovars Virchow (n = 3), Kentucky (n = 1), and Newport (n = 1), in two of three strains of the serovar Infantis, and in one of two strains of the serovar Stanley. All five blood isolates were assigned to the serovar Enteritidis and one of them showed resistance to ciprofloxacin. Of 79 resistant strains, 26.6% showed resistance to ampicillin only and 24.1% to ciprofloxacin only, with multidrug resistance, i.e. resistance to three or more antibiotics, confirmed in 43.0% of strains., Conclusion: Despite a relatively low prevalence of resistance to the antibiotics tested among 637 study strains, the following alarming findings were made: Detection of Salmonella enterica strains resistant to ciprofloxacin as the drug of choice or to higher generation cephalosporins and multidrug resistance revealed in two thirds of the strains of the serovar Typhimurium and in all but one strains of its monophasic variant 4,[5],12:i:-.

Mutagenic activities of feedstuffs and bovine milk were investigated by the Ames test in two districts of the Czech Republic (Teplice and Prachatice), differing in the levels of industrial pollution. Salmonella typhimurium strains TA 98 and TA 100 with or without metabolic activation were used in the tests. Samples of currently fed feedstuffs and milk were collected in both districts in the spring 1992, autumn 1992, spring 1993, and autumn 1993. The Teplice and Prachatice sets included 12 and 11 representative samples, respectively. The samples were rinsed and extracted with acetone and methanol. Thus each sample was divided into four separate samples. The total number of revertants obtained in the industrial district Teplice was significantly higher than the corresponding value for the Prachatice district. Some between-the-seasons differences were also found within each of the two districts. The strain TA 98 proved to be more sensitive in the mutagenicity tests than the strain TA 100. Thirty-eight and thirty-one milk samples were collected in the districts Teplice and Prachatice, respectively. The overall evaluation demonstrated a significant between-the-districts difference in the total number of revertants induced by the milk samples in the strains TA 98 and TA 100.

Single pilot examinations of mutagenicity of stable dust and drinking water were made on three swine farms (D., M., T.) and one cattle farm (N.) in the district of Hodonín in summer 1994. The mutagenicity was examined by the Ames test using the indicator strains Salmonella typhimurium TA 98 and TA 100 with (+S9) or without (-S9) metabolic activation. At the same time the contents of selected pesticides (PES) and polychlorinated biphenyls (PCB) in stable dust and drinking water and that of polycyclic aromatic hydrocarbons in stable dust were determined. Increased mutagenicity was demonstrated in drinking water (strain TA 98 with metabolic activation; index Rt/Rk 3.6-7.7) and stable dust (strain TA 100 with metabolic activation; index Rt/Rk 2.2) collected on the swine farm M. High contents of PAH (8.246 mg/kg) and PCB (0.263 mg/kg) were also found in the dust samples collected on this farm. Only drinking water showed mutagenic activity (strain TA 98 without metabolic activation; index Rt/Rk 2.6) on the swine farm D. On both the farms, the number of revertants was dose-dependent. Increased content of PAH (2.553 mg/kg) was also demonstrated on the dust samples collected on the farm D. No significant increase (twofold or higher when compared with negative controls) of mutagenic activity of stable dust or drinking water was demonstrable on the swine farm T. and the cattle farm N. Substances responsible for the mutagenicity of drinking water on the farms D. and M. have not yet been identified. Anyway, the increase of mutagenicity of stable dust and drinking water should be taken as a warning that mutagens that can jeopardise animal and human health have penetrated into the stable environment.

We studied the biological effects of the factors released into the culture medium by the lymphocytes from animals sensitized with testicular antigen. The supernatants from cultures of these lymphocytes were active in vitro in the migration inhibition tests because they transferred the sensitivity to normal spleen cells. In vivo, they transferred aspermatogenesis in the allogeneic and xenogeneic system. The results suggest a specific effect on the behaviour of macrophages rather than a direct cytotoxic effect of the active factors.

Repeated intraperitoneal administration of F9 teratocarcinoma stem cells (first dose of 3.8 X 10(8) + 3 doses of 7.5 X 10(8) cells at two-week intervals) to guinea pigs starting from birth prevented in more than one third of them (in 10 out of 28) the induction of autoimmune aspermatogenesis by subsequent immunization with spermatogenic cells emulsified with FCA. Cytotoxic and immunofluorescent activities against spermatogenic cells were similar in groups of males after tolerance induction and subsequent immunization and of males immunized only. However, these two groups differed substantially in serological activities against F9 cells which were significantly higher in the former group. The results are discussed in connection with the establishment of the blood-testis barrier which may have resulted in the absence of autotolerance towards spermatogenic cell antigens.

The synthetic steroid antiandrogen, cyproterone acetate, and the androgen, testosterone isobutyrate, were injected subcutaneously into adult male and female guinea pigs of two outbred strains (laboratory coloured and albino Pirbright-Harley stocks). Cyproterone acetate was given as 1, 10 and 20 daily 5-mg doses (body-weight matched with immunosuppressively effective doses in mice) and as 30 doses of 15 micrograms/100 g b.w. (body-weight matched with those used in the long-term human male contraception), testosterone as 1 and 10 doses of 5 mg/100 g b.w. The guinea pigs of the two stocks used showed different sensitivity: with the same doses of CA albino guinea pigs compared to the coloured ones declined in weight, had lower viability, reduced thymus weight, diminished capacity for SRBC haemolysin formation, a lower testes weight and inhibited spermatogenesis. Both stocks reacted by similar lymphopoenia, however. Testosterone neither inhibited haemolysin formation nor produced lymphopoenia but induced a more marked reduction of thymus weight than did CA and, in addition, produced greater depletion of cortex lymphocytes in albino guinea pigs. The thymus of albino guinea pigs was more sensitive to testosterone than to cyproterone acetate. Sexual dimorphism was apparent in some criteria in albino guinea pigs following cyproterone acetate and testosterone. Cyproterone acetate in the lowest doses had no inhibitory effect on thymus or SRBC formation but also did not affect spermatogenesis in albino guinea pigs. The hitherto accepted classification of animal species according to which guinea pigs (and also man) belong to steroid-resistant species is discussed and questioned, and the potential risks of application of sexual steroids in male contraception are stressed.

The efficiency of mercurascan on prolongation of skin allograft survival was found to depend on the sex of experimental animals. Long-term treatment of the recipients by MSC in the mouse strain combination B10--B10.LP (donor X recipient, difference in non-H-2 loci) was more efficient in females than in males. The immunosuppressive effect of MSC was weak. MSC had no effect on the survival time of skin or heart allografts in a strain combination with limited H-2 differences [B10.D2--M(504)]. The effect of MSC on the cell membrane was followed in vitro by measurement of the rate of H-2 antigen redistribution on lymphoid cells of animals treated in vivo by MSC. The rate of redistribution on lymphoid cells from MSC-treated females was decreased; no effect was observed in the case of cells from treated males.

The expression, properties and relationship of two mouse embryonic antigens (TEC-1 and TEC-2), which are defined by monoclonal antibodies, were investigated in the epididymis of four rodent species. Absorption analysis, indirect immunofluorescence microscopy and immunohistochemistry revealed that all the species studied contained in their epididymides, but not in testes, either TEC-1 (Chinese hamster), TEC-2 (guinea pigs, rats) or both TEC-1 and TEC-2 (mice) antigens. In an indirect immunofluorescence assay, the antigens were found on spermatozoa isolated from caudae epididymides of guinea pigs, rats and Chinese hamsters but not mice. On the other hand, the TEC-2 antigen, which is expressed on mouse eggs, was not detected on eggs from the other species studied. Immunolabeling of epididymal extracts separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that both epididymal antigens have apparent molecular weights of greater than 200,000. In guinea pigs, rats and mice, the antigens were detected by a two-site sandwich radioantibody-binding assay in which the antigen is immobilized and detected with the same antibody; this indicates that several antigenic determinants were present on the same carrier. In mice, some carriers seem to express both TEC-1 and TEC-2 epitopes. In Chinese hamsters, TEC-1 antigen was only detected by the solid-phase assay, suggesting that in this species there are markedly fewer antigenic determinants per carrier molecule. Interspecies differences in the activities of epididymal glycosyltransferases and/or glycosidases appear to be the biochemical mechanism of the species-specific expression of these antigens.

The effect of certain polymers on the course of immune interaction has been well known although its mechanism at the cellular level remains obscure. We thus affected cells in vitro with two of such substances, CS and PVP, and followed their behaviour in various assays. It was shown that in this way the agglutinability of mouse erythrocytes with H-2 antibodies or of mouse lymphocytes with threshold doses of Con A could be enhanced, antibody-induced capping of H-2 antigens on lymphocytes accelerated and PHA-induced stimulation of mouse lymphocytes inhibited. The possible mechanisms of these changes putatively mediated through the effect on the cell membrane or cell coat are discussed.

Mice immunized with teratocarcinoma F9 cells or human blood group substances A, B or H exhibited significant inhibition of spermatogenesis comparable to the inhibition induced by immunization with testicular cells. All these immunization schemes resulted in the production of antibodies which recognize antigens common to F9 and spermatogenic cells. In addition to these antigens, both anti-F9 and anti-ABH sera also recognize antigens which are specific for F9 cells. One of them was identified as SSEA-1. These results support the hypothesis that oncofetal F9 antigens are carbohydrate structures, which may play an important role in spermatogenic cell differentiation.